Surya Bhatt, MD: Findings on Dupilumab for Patients with COPD, Type 2 Inflammation

Surya Bhatt, MD

Credit: X (Twitter)

The US Food and Drug Administration (FDA) recently accepted the supplemental Biologics License Application (sBLA) for dupilumab treatment of adult patients with uncontrolled chronic obstructive pulmonary disease (COPD) and type 2 inflammation.¹

The drug is a fully human monoclonal antibody designed to inhibit interleukin (IL)-13 and IL-4 signaling pathways, and it does not function as an immunosuppressant. Other indications for the drug have included prurigo nodularis, atopic dermatitis, asthma, and chronic spontaneous urticaria (CSU).

The FDA target action date for the drug’s use in COPD is slated for June 27, 2024. In a recent interview with the HCPLive editorial team, Surya Bhatt, MD, spoke on his team’s research into dupilumab that had led to the FDA’s sBLA acceptance.

Bhatt is known for his work in the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Alabama at Birmingham. He is also the medical director of the UAB Pulmonary Function and Exercise Physiology Lab.

HCPLive: What would you say were some of the key findings or insights from the research you were involved in that contributed to the sBLA for dupilumab as an add-on maintenance treatment for COPD?

Bhatt: There are 2 pivotal trials, BOREAS and NOTUS, both looking at the efficacy and safety of dupilumab for patients with high exacerbation risk and with evidence of type 2 inflammation which was measured as blood eosinophil counts greater than or equal to 300 cells per microliter, while on triple inhaled therapy.

Both studies showed a significant reduction in exacerbation frequency over and above what was seen with triple therapy, which is the maximum standard inhaled therapy available right now.

HCPLive: What were any particular breakthroughs that your team observed over the course of the 2 trials?

Bhatt: I think the biggest breakthrough is the very large reduction in exacerbation frequency for patients who continue to suffer exacerbations despite being on triple therapy. Historically, almost half the patients who are on maximal inhaled therapy continue to suffer from exacerbations. So this effect size is truly remarkable for these patients who will benefit significantly.

HCPLive: Considering its potential approval as the first biologic therapy for COPD, and the first new treatment approach in over a decade, what implications do you foresee for patients with uncontrolled COPD and how might it impact the current treatment paradigm?

Bhatt: I think we will see a large shift in the treatment landscape. The effect of exacerbations is not just on short term morbidity, in terms of how the patient feels, but also has long term effects in terms of disease progression. There are significant data to suggest that exacerbations result in more lung function decline, and also in progression of emphysema.

So by preventing these exacerbations, although this was tested in the trials themselves, I think there is a large potential to decrease the rate of progression of COPD. Also, exacerbations have direct bearing on quality of life for the patients, which was demonstrated in the studies, and also on lung function, which were also demonstrated in the studies.

HCPLive: In your opinion, then, given some of these findings, what sets dupilumab apart from existing treatments for COPD, particularly in terms of safety, efficacy, and the mechanism of action?

Bhatt: All the treatments that exist right now are predominantly directed towards symptom relief in the form of bronchodilators. The only exception is inhaled corticosteroids, which results in a nonspecific suppression of inflammation in the lungs. Dupilumab has a much broader effect on type 2 inflammation and directly modulates several pathways of disease pathogenesis in the lungs.

So in that sense, I think it is potentially a disease modifier. There are several speculated mechanisms of action, including reduction of mucus production, decreasing the contractility of airway smooth muscles thereby enhancing bronchodilation.

The mode of administration is also different. All the treatments right now are mostly inhaled therapies except a couple of exceptions such as azithromycin and roflumilast, which are given orally. This is a subcutaneous mode of administration, and it's only administered once every 2 weeks. So this does open up a different way of administering treatments which have long lasting effects.

HCPLive: If dupilumab receives approval from the FDA, what do you believe would be the broader significance of the decision as far as the field of respiratory medicine in general?

Bhatt: If approved, this will be the first biologic approved for the treatment of COPD. This will be highly impactful because there are several millions of people with COPD who suffer with exacerbations. So this will open up a whole new avenue for treatment of these patients.

There was a 34% reduction in exacerbation frequency. Although effect sizes across trials are not directly comparable, this is the largest effect size we've seen in any COPD trial. I think that's truly remarkable.

The quotes contained in this interview were edited for clarity.

References

1. ^{Smith T. FDA Accepts sBLA for Priority Review of Dupilumab for Uncontrolled COPD. HCPLive. February 23, 2024. https://www.hcplive.com/view/fda-accepts-sbla-for-priority-review-of-dupilumab-for-uncontrolled-copd. Date accessed: February 27, 2024.}